Sin Nombre virus: Infectious substances pathogen safety data sheet

Section I – Infectious agent

Name

Sin Nombre virus

Agent type

Virus

Taxonomy

Family

Hantaviridae

Genus

Orthohantavirus

Species

sinnombreense

Synonym or cross-reference

Sin Nombre virus (SNV) is a New World hantavirus that causes hantavirus pulmonary syndrome (HPS), which is also known as hantavirus cardiopulmonary syndrome (HCPS)^{Footnote 1Footnote 2}.

Characteristics

Brief description

SNV has a single-stranded, negative-sense RNA genome, consisting of three segments: small (S), medium (M), and large (L)^{Footnote 3}. The S segment is 2.06 kb in length and encodes the nucleocapsid protein, while the M segment is 3.70 kb and encodes the glycoprotein precursor that is cleaved to form the two envelope glycoproteins, Gn and Gc. The L segment is 6.56 kb in length and encodes the RNA-dependent RNA polymerase (RdRp). The segments form helical nucleocapsids once surrounded by nucleoprotein^{Footnote 1Footnote 4}. The virions of SNV are enveloped and roughly spherical with a mean diameter of 112 nm. SNV has a range of morphologies including round, tubular, and irregular^{Footnote 5}. The round and tubular particles have an average diameter of 90 nm and 85 nm, respectively, and the tubular particles measure 180 nm in length, on average.

Properties

The human integrin, ɑVβ3, has been proposed as the cellular receptor for the attachment of SNV to the host cell^{Footnote 4}. Entry is facilitated by other cell surface proteins including the decay-accelerating factor, CD55, and the complement receptor, gC1qR/p32, and this process might involve micropinocytosis. Following entry, the virus will travel to early or late endosomes where the glycoprotein precursor, Gn/Gc, will undergo a pH-dependent conformational change, which allows for the release of the viral genome. Replication of the genome and translation of viral proteins takes place in the cytoplasm. The glycoprotein precursor becomes cleaved in the endoplasmic reticulum (ER) to form the Gn and Gc glycoproteins. They then traffic to the Golgi apparatus where they oligomerize to form heterodimers. SNV is thought to assemble at the plasma membrane where the Gn/Gc octameric spikes aid in budding from the host cell.

Section II – Hazard identification

Pathogenicity and toxicity

There are four phases associated with HPS: febrile prodrome, cardiopulmonary, diuresis, and convalescence^{Footnote 6}. The prodrome period lasts from three to five days and symptoms include sudden fever, chills, muscle aches and pains, and malaise^{Footnote 7Footnote 8}. Loss of appetite, nausea, and vomiting have also been reported at this stage. One estimate suggests that approximately 50% of patients may seek medical care during this period, but patients are often sent home due to lack of specific findings^{Footnote 7}. A key marker of disease progression is the detection of thrombocytopenia as the degree of platelet depletion is associated with death^{Footnote 9}. The next phase involves cardiopulmonary symptoms, including a mild, nonproductive cough and progressive shortness of breath^{Footnote 7Footnote 8}. This stage may require intubation within the first few hours, intensive cardiopulmonary care, and close observation for hypoxemia and shock^{Footnote 10}. The disease can progress rapidly and death may occur within hours or days^{Footnote 9}. However, severe pulmonary disease or respiratory failure do not occur in all cases of SNV infection^{Footnote 11}. Survival past the cardiopulmonary phase is associated with sudden onset of the diuresis phase and is generally followed with rapid clinical improvement^{Footnote 6Footnote 10}. The convalescent phase involves persistent fatigue and shortness of breath upon exertion and may last three to four weeks or longer^{Footnote 6}. In Canada, approximately 25% of HPS cases caused by SNV are fatal^{Footnote 12}.

Epidemiology

SNV is distributed throughout North America, where it accounts for the majority of HPS cases^{Footnote 13Footnote 14}. However, HPS can also be caused by other viruses circulating in the rodent population in North America, such as Monongahela virus, Bayou virus, Black Creek Canal virus and New York virus^{Footnote 14}. Approximately 1000 cases of HPS have been confirmed in North America, and as of 2020, 143 laboratory-confirmed cases of HPS caused by SNV were reported in Canada^{Footnote 2}. Peaks in the number of reported cases typically occur between May and June, which is thought to be driven by increases in the population of deer mice and human contact with environments contaminated by rodent excreta^{Footnote 2}. Infections with SNV are generally sporadic and independent, but two outbreaks as well as various clusters of cases affecting communities and households have been reported^{Footnote 2Footnote 15}. The first outbreak occurred in 1993 in the Four Corners region of the United States where at least 24 cases of SNV infection were confirmed with a reported fatality rate of 50%^{Footnote 9}. The second outbreak occurred in 2012 in Yosemite National Park, California, involving 10 individuals with laboratory-confirmed SNV infections and a case fatality rate of 30%^{Footnote 15}.

Host range

Natural hosts

Humans are considered dead-end hosts^{Footnote 16}. Animal hosts include deer mice (Peromyscus maniculatus) and other rodents (Peromyscus boylii, Mus musculus, Neotoma mexicana, and Tamias minimus)^{Footnote 17}.

Other hosts

Hamsters and rhesus macaques have been experimentally infected^{Footnote 18Footnote 19}.

Infectious dose

Unknown.

Incubation period

The incubation period of SNV ranges from 14 to 17 days, but has also been documented to extend to 51 days^{Footnote 7Footnote 8}.

Communicability

The preferred mode of transmission of SNV in humans is through inhalation of aerosolized secreta and excreta of infected mice, particularly from the primary reservoir host, deer mice (Peromyscus maniculatus)^{Footnote 2Footnote 13Footnote 17}. Ingestion of food contaminated by the urine, feces, or saliva of infected rodents is also thought to be a mode of transmission for hantaviruses. Since SNV is transmitted via aerosols, it is possible that the virus could spread through contact with mucous membranes. Transmission through bites of rodents has been documented for other hantaviruses, but is quite rare. Transmission between rodents occurs through contact with bodily fluids, confrontations between animals, or during grooming events^{Footnote 3}.

Section III – Dissemination

Reservoir

Reservoirs include deer mice (Peromyscus maniculatus) and other rodents (Peromyscus boylii, Mus musculus, Neotoma mexicana, and Tamias minimus)^{Footnote 17}.

Zoonosis

Infected rodents spread the virus to humans through contaminated excreta and/or secreta^{Footnote 2}.

Vectors

None.

Section IV – Stability and viability

Drug susceptibility/resistance

There are no approved drugs available to treat SNV infection, but the antivirals, favipiravir and ribavirin, have demonstrated some effectiveness in in-vitro and in-vivo models^{Footnote 20}.

Susceptibility to disinfectants

Similar to other enveloped viruses, hantaviruses are inactivated by detergents, hypochlorite solutions, and organic solvents^{Footnote 21}. A related orthohantavirus, Hantaan virus (HTNV), was shown to be inactivated after incubation in methanol for 8 minutes, 1% paraformaldehyde for 20 minutes, or acetone/methanol (1:1) for 10 minutes^{Footnote 22}.

Physical inactivation

Inactivation measures for SNV are unknown, but enveloped viruses can be inactivated by a temperature of 60°C for 30 minutes^{Footnote 20}. Further, UV irradiation was shown to inactivate HTNV in infected Vero E6 cells after 3 minutes at 312 nm^{Footnote 21}.

Survival outside host

The viability of SNV outside of the host is unknown, but one study found that other orthohantaviruses, Puumala virus and Tula virus, remained infectious for 12 to 15 days at room temperature in contaminated bedding, 5 to 11 days in cell culture medium at room temperature, and 18 days in cell culture medium at 4°C^{Footnote 23}.

Section V – First aid/medical

Surveillance

SNV can be detected in serum, whole blood, and plasma through reverse transcriptase quantitative polymerase chain reaction (RT-qPCR)^{Footnote 17}. Enzyme-linked immunosorbent assays (ELISA) can also be used to detect IgG or IgM antibodies in the sera^{Footnote 3}.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook.

First aid/treatment

There is no specific treatment for SNV infection or HPS^{Footnote 2Footnote 24}. Supportive care, often in ICU, is recommended, as well as supplemental oxygen for hypoxia if the disease enters the cardiopulmonary phase^{Footnote 3}. Due to the risk of edema, the amount of fluids administered should be monitored.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the Canadian Biosafety Handbook.

Immunization

There are no vaccines currently available; however, potential candidates are being studied such as a SNV DNA vaccine that was shown to elicit high-titer neutralizing antibodies in-vivo^{Footnote 3Footnote 25}.

Note: More information on the medical surveillance program can be found in the Canadian Biosafety Handbook, and by consulting the Canadian Immunization Guide.

Prophylaxis

There are no pre- or post-exposure measures available to prevent infection or disease with SNV^{Footnote 2Footnote 24}.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the Canadian Biosafety Handbook.

Section VI – Laboratory hazard

Laboratory-acquired infections

A laboratory worker at the United States Army Medical Research Institute of Infectious Disease (USAMRIID) was exposed to 7 ml of cell culture supernatant with a high concentration of SNV^{Footnote 26}. She was treated with 400 mg of oral ribavirin for 20 days. She was asymptomatic and RT-PCR and IgM ELISA assays were negative.

Note: Please consult the Canadian Biosafety Standard and Canadian Biosafety Handbook for additional details on requirements for reporting exposure incidents.

Sources/specimens

SNV can be detected in serum, whole blood, or plasma^{Footnote 17}.

Primary hazards

Inhalation of infectious material in animal waste is the primary hazard associated with exposure to SNV^{Footnote 13Footnote 17}.

Special hazards

None.

Section VII – Exposure controls/personal protection

Risk group classification

Orthohantavirus sinnombreense is a Risk Group 3 Human Pathogen, a Risk Group 1 Animal Pathogen, and a Security Sensitive Biological Agent (SSBA)^{Footnote 27}.

Containment requirements

Containment Level 3 facilities, equipment, and operational practices outlined in the Canadian Biosafety Standard for work involving infectious or potentially infectious materials, animals, or cultures are required.

Note that there are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving SSBAs.

Protective clothing

The applicable Containment Level 3 requirements for personal protective equipment and clothing outlined in the Canadian Biosafety Standard are to be followed. At minimum, use of full body coverage dedicated protective clothing, dedicated protective footwear and/or additional protective footwear, gloves when handling infectious materials or animals, face protection when there is a known or potential risk of exposure to splashes or flying objects, respirators when there is a risk of exposure to infectious aerosols, and an additional layer of protective clothing prior to work with infectious materials or animals.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone must be documented.

Other precautions

All activities involving open vessels of pathogens are to be performed in a certified biological safety cabinet (BSC) or other appropriate primary containment device. Centrifugation of regulated materials to be carried out in sealed safety cups or rotors that are unloaded in a BSC or other primary containment device using a mechanism that prevents their release. The use of needles, syringes, and other sharp objects are to be strictly limited. Additional precautions must be considered with work involving animals or large scale activities.

Section VIII – Handling and storage

Spills

Allow aerosols to settle. Wearing personal protective equipment, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time between the surface and the disinfectant before clean up (Canadian Biosafety Handbook).

Disposal

Regulated materials, as well as all items and waste to be decontaminated at the containment barrier prior to removal from the containment zone, animal room, animal cubicle, or post mortem room. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the infectious material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (Canadian Biosafety Handbook).

Storage

The applicable Containment Level 3 requirements for storage outlined in the Canadian Biosafety Standard are to be followed. Primary containers of regulated materials removed from the containment zone are to be stored in a labelled, leak-proof, impact-resistant secondary container, and kept either in locked storage equipment or within an area with limited access.

Containers of SSBAs stored outside the containment zone must be labelled, leakproof, impact resistant, and kept in locked storage equipment that is fixed in place (i.e., non-movable) and within an area with limited access.

An inventory of RG3 and SSBA toxins in long-term storage, to be maintained and to include:

• specific identification of the regulated materials
• a mechanism that allows for the detection of a missing or stolen sample in a timely manner

Section IX – Regulatory and other information

Canadian regulatory information

Controlled activities with Orthohantavirus sinnombreense require a Pathogen and Toxin licence issued by the Public Health Agency of Canada.

Note that there are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving SSBAs.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

• Human Pathogens and Toxins Act and Human Pathogens and Toxins Regulations
• Transportation of Dangerous Goods Act and Transportation of Dangerous Goods Regulations
• National notifiable disease (human)
• Hantavirus infection or hantavirus pulmonary syndrome is a notifiable disease in every province and territory in Canada

Last file update

August, 2024

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, directives and standards applicable to the import, transport, and use of pathogens and toxins in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

Copyright ^© Public Health Agency of Canada, 2024, Canada